GALC (galactocerebrosidase / galactosylceramidase; EC 3.2.1.46) is a lysosomal glycoside hydrolase of the GH59 family that catabolizes galactolipids. It hydrolyzes the terminal galactose from galactosylceramide (galactocerebroside) to yield ceramide plus D-galactose, and also hydrolyzes galactosylsphingosine (psychosine) and related galactolipids. Acting at acidic pH in the lysosome/lysosomal lumen, the soluble enzyme depends on the lipid-transfer protein saposin A (derived from prosaposin, PSAP), which presents the membrane-embedded glycosphingolipid substrate to the GALC active site. Galactosylceramide is a major lipid of the myelin sheath, so GALC is central to myelin glycosphingolipid turnover. Loss of GALC activity causes Krabbe disease (globoid cell leukodystrophy), an autosomal recessive lysosomal storage disorder in which accumulation of the cytotoxic substrate psychosine drives demyelination and neurodegeneration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004336 galactosylceramidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAN-GO) transfer of the defining molecular function of GALC. GALC is a GH59 galactosylceramidase (EC 3.2.1.46) that hydrolyzes the terminal galactose from galactosylceramide; this is the biochemically demonstrated core activity of the human enzyme. Reason: This is the correct, specific molecular function for GALC and represents its core catalytic activity. It is directly supported by biochemistry on the purified human enzyme and cDNA expression, and is consistent across the phylogenetic tree. Supporting Evidence: PMID:8399327 Galactocerebrosidase (GALC, EC 3.2.1.46) was purified from human urine file:human/GALC/GALC-uniprot.txt Hydrolyzes the galactose ester bonds of glycolipids such as |
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic transfer of lysosomal localization. GALC is a soluble acid hydrolase that acts in the lysosome; UniProt subcellular location is Lysosome and the enzyme has an acidic pH optimum consistent with lysosomal function. Reason: Lysosome is the correct site of action for GALC and is well supported. Retained as a core localization for this lysosomal enzyme. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in PMID:7601472 catalyzes the lysosomal hydrolysis of specific galactolipids |
| GO:0006683 galactosylceramide catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic transfer of the core biological process. By hydrolyzing galactosylceramide to ceramide and galactose, GALC executes the lysosomal galactosylceramide catabolic process. Reason: This is the precise biological process for GALC's catalytic activity and is its core role. Retained as a core function. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in PMID:15657896 galactosylcerebroside to ceramide |
| GO:0004336 galactosylceramidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (ARBA/InterPro/RHEA/EC) assignment of galactosylceramidase activity, mapping GALC (GH59 family, EC 3.2.1.46, RHEA:14297) to its defining molecular function. Reason: The electronic mapping is correct and matches the experimentally verified core activity; the same term is independently supported by IDA and IBA. Supporting Evidence: file:human/GALC/GALC-uniprot.txt Belongs to the glycosyl hydrolase 59 family |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCellular-location keyword mapping to lysosome, consistent with the curated UniProt subcellular location (Lysosome) for this acid hydrolase. Reason: Lysosomal localization is correct and independently supported (IBA, TAS). Kept as a core localization. Supporting Evidence: PMID:7601472 catalyzes the lysosomal hydrolysis of specific galactolipids |
| GO:0006683 galactosylceramide catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (ARBA/InterPro) assignment of galactosylceramide catabolic process, the precise biological process executed by GALC's hydrolase activity. Reason: Correct electronic mapping matching the experimentally supported core process; also supported by IDA, IBA and ISS. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in |
| GO:0006683 galactosylceramide catabolic process | IDA PMID:15657896 Implications of galactocerebrosidase and galactosylcerebrosi... | ACCEPT | Summary: Galactosylceramide catabolic process supported by a review of GALC/GalCer metabolism in cancer, which describes GALC as the enzyme degrading galactosylcerebroside to ceramide. The biology (GALC breaks down galactosylceramide) is correct. Reason: The annotated process is the correct core process for GALC. The cited reference is a review (annotated IDA), so it is not the strongest primary evidence, but the same process is robustly supported by primary biochemistry (PMID:8281145, PMID:8399327) and by IBA. Per curation policy, the experimental annotation is retained rather than removed. Supporting Evidence: PMID:15657896 the enzyme responsible for degrading PMID:15657896 galactosylcerebroside to ceramide |
| GO:0004336 galactosylceramidase activity | IDA PMID:8281145 Cloning and expression of cDNA encoding human galactocerebro... | ACCEPT | Summary: Direct assay of galactosylceramidase activity. The human GALC cDNA was cloned and expressed in COS-1 cells, yielding GALC enzyme activity; the enzyme is defined as responsible for lysosomal catabolism of galactosylceramide. This is the primary experimental basis for the core molecular function. Reason: Direct experimental support (cDNA expression conferring GALC activity) for the core catalytic function; represents the defining molecular function of the gene. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in |
| GO:0004336 galactosylceramidase activity | IDA PMID:8281145 Cloning and expression of cDNA encoding human galactocerebro... | ACCEPT | Summary: Direct assay of galactosylceramidase activity (duplicate GOA record from a different assigning group, same term/evidence/reference). Human GALC cDNA expression confers GALC enzyme activity, defining the core molecular function. Reason: Duplicate of the direct-evidence galactosylceramidase-activity annotation; same correct core molecular function. Retained. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in |
| GO:0036021 endolysosome lumen | IC PMID:27498570 Endolysosomes Are the Principal Intracellular Sites of Acid ... | KEEP AS NON CORE | Summary: Curator inference (IC) placing GALC's activity in the endolysosome lumen, derived from its acid-hydrolase molecular function (GO:0004336) together with the general finding that endolysosomes are the principal intracellular sites of acid hydrolase activity. The cited paper is a general endolysosome study and does not assay GALC specifically. Reason: Reasonable and biologically consistent refinement of the lysosomal localization, but it is an inference from a general acid-hydrolase study rather than GALC-specific evidence. The core, best-supported localization for GALC is the lysosome/lysosomal lumen; kept as a non-core, more granular localization. Supporting Evidence: PMID:27498570 endolysosomes are the principal organelles in which substrates are hydrolyzed |
| GO:0036021 endolysosome lumen | IC PMID:29323104 The mechanism of glycosphingolipid degradation revealed by a... | KEEP AS NON CORE | Summary: Curator inference (IC) that GALC is active in the endolysosome lumen, supported by the GALC-SapA complex study showing that GALC-mediated glycosphingolipid degradation occurs at low pH equivalent to the late-endosomal/lysosomal (endolysosomal) compartment and requires saposin A. Reason: The endolysosomal context is well grounded in this GALC-specific structural and biochemical study, but at the granularity used by this project the core localization is the lysosome/lysosomal lumen. Retained as a non-core, more granular localization. Supporting Evidence: PMID:29323104 responsible for the removal of the terminal galactose from the glycosphingolipid galactocerebroside PMID:29323104 This enzyme requires the saposin SapA for lipid |
| GO:0046479 glycosphingolipid catabolic process | TAS Reactome:R-HSA-9840310 | KEEP AS NON CORE | Summary: Reactome pathway annotation placing GALC in glycosphingolipid catabolism. Galactosylceramide is a glycosphingolipid, so this is a correct but broader-than-precise parent process relative to galactosylceramide catabolic process. Reason: Correct but more general than the precise core term (GO:0006683 galactosylceramide catabolic process). Retained as a valid non-core, higher-level pathway annotation. Supporting Evidence: PMID:29323104 responsible for the removal of the terminal galactose from the glycosphingolipid galactocerebroside |
| GO:0030149 sphingolipid catabolic process | IDA PMID:8281145 Cloning and expression of cDNA encoding human galactocerebro... | KEEP AS NON CORE | Summary: Sphingolipid catabolic process, a broad parent of the precise galactosylceramide catabolic process. GALC catabolizes galactosylceramide (a glycosphingolipid) and galactosylsphingosine, so it acts in sphingolipid catabolism. Reason: Correct but less specific than the core term (GO:0006683 galactosylceramide catabolic process). Retained as a valid non-core, higher-level process annotation. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in |
| GO:0004336 galactosylceramidase activity | TAS Reactome:R-HSA-1606564 | ACCEPT | Summary: Reactome traceable assertion of galactosylceramidase activity (reaction "GALC hydrolyzes GalCer"), matching the defining, experimentally verified core molecular function of GALC. Reason: Correct core molecular function, independently supported by IDA and IBA. Retained as core. Supporting Evidence: PMID:8399327 Galactocerebrosidase (GALC, EC 3.2.1.46) was purified from human urine |
| GO:0004336 galactosylceramidase activity | IDA PMID:8399327 Galactocerebrosidase from human urine: purification and part... | ACCEPT | Summary: Direct biochemical characterization of galactosylceramidase activity. GALC (EC 3.2.1.46) was purified ~176,000-fold from human urine (and brain, placenta) with an acidic pH optimum (4.0-4.4) and KM=10 uM for N-acyl-beta-D-galactosylsphingosine, directly demonstrating the enzyme's activity. Reason: Strong direct experimental evidence for the core molecular function of GALC on the purified human enzyme. Retained as core. Supporting Evidence: PMID:8399327 Galactocerebrosidase (GALC, EC 3.2.1.46) was purified from human urine |
| GO:0006683 galactosylceramide catabolic process | IDA PMID:8399327 Galactocerebrosidase from human urine: purification and part... | ACCEPT | Summary: Galactosylceramide catabolic process supported by direct characterization of the purified human enzyme, which is deficient in Krabbe disease and cleaves galactolipid substrates. This is the precise core biological process for GALC. Reason: Direct experimental support for the core catabolic process of GALC. Retained as core. Supporting Evidence: PMID:8399327 Galactocerebrosidase (GALC, EC 3.2.1.46) was purified from human urine |
| GO:0004336 galactosylceramidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of galactosylceramidase activity from the mouse ortholog (UniProtKB:P54818). GALC is a conserved GH59 galactosylceramidase. Reason: The ortholog-based transfer is correct and redundant with the direct experimental (IDA) and IBA support for the same core molecular function. Supporting Evidence: file:human/GALC/GALC-uniprot.txt Belongs to the glycosyl hydrolase 59 family |
| GO:0006683 galactosylceramide catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of galactosylceramide catabolic process from the mouse ortholog (UniProtKB:P54818), matching GALC's precise core biological process. Reason: Correct ortholog-based transfer, redundant with direct (IDA) and IBA support for the same core process. Supporting Evidence: PMID:8281145 responsible for the lysosomal catabolism of galactosylceramide, a major lipid in |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1606564 | ACCEPT | Summary: Reactome traceable assertion localizing GALC to the lysosomal lumen, the compartment where the soluble acid hydrolase acts on its substrate. Reason: Correct and specific localization of this soluble lysosomal hydrolase to the lysosomal lumen. Retained as a core localization. Supporting Evidence: PMID:7601472 catalyzes the lysosomal hydrolysis of specific galactolipids |
| GO:0005764 lysosome | TAS PMID:7601472 Structure and organization of the human galactocerebrosidase... | ACCEPT | Summary: Lysosome localization asserted from the literature. The GALC gene-structure paper describes the enzyme as catalyzing lysosomal hydrolysis of galactolipids, consistent with a lysosomal acid hydrolase. Reason: Correct core localization, independently supported by IBA and Reactome TAS. Retained as core. Supporting Evidence: PMID:7601472 catalyzes the lysosomal hydrolysis of specific galactolipids |
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